What is the treatment for bacteremia caused by vancomycin-resistant Enterococcus (VRE) faecalis?

Treatment for Bacteremia Caused by Vancomycin-Resistant Enterococcus faecalis

Linezolid 600 mg IV or PO every 12 hours is the first-line treatment for bacteremia caused by vancomycin-resistant Enterococcus faecalis, with high-dose daptomycin (8-12 mg/kg/day) being an effective alternative, especially at doses ≥9 mg/kg. 1

First-Line Treatment Options

Linezolid

• FDA-approved specifically for vancomycin-resistant Enterococcus faecium infections, including cases with concurrent bacteremia 2
• Recommended dosage: 600 mg IV or PO every 12 hours (strong recommendation, low quality of evidence) 1
• Demonstrated clinical efficacy with overall microbiological and clinical cure rates of 86.4% and 81.4%, respectively 1
• Can be administered orally or intravenously with excellent bioavailability, allowing for convenient step-down therapy 2
• Treatment duration depends on the site of infection and clinical response 1

High-Dose Daptomycin

• Recommended at doses of 8-12 mg/kg/day for VRE bacteremia (weak recommendation, low quality of evidence) 1
• Higher doses (≥9 mg/kg) are associated with better survival compared to lower doses (6-9 mg/kg) 3
• Can be used in combination with β-lactams (penicillins, cephalosporins, or carbapenems) for potential synergistic effect 1
• Despite lacking FDA approval specifically for VRE infections, daptomycin has demonstrated better in vitro bactericidal activity against VRE than other agents including vancomycin and quinupristin-dalfopristin 1

Comparative Efficacy

• Meta-analyses comparing linezolid and daptomycin have shown conflicting results 1, 4
• Some studies suggest lower mortality with linezolid compared to daptomycin (32.8% vs. 35.7%) 1, 4
• However, when higher-dose daptomycin (≥9 mg/kg) is used, there appears to be no significant survival benefit of linezolid over daptomycin 3
• Microbiological cure rates are comparable between daptomycin and linezolid (93% vs. 91%) 1

Special Considerations

Combination Therapy

• Daptomycin combined with β-lactams has shown improved outcomes in some studies 1
• Higher daptomycin MIC (3-4 mg/mL) was associated with treatment failure, but this effect was mitigated when daptomycin was combined with β-lactams 1
• Combinations with non-β-lactams (gentamicin, linezolid, rifampin, tigecycline) have been reported but require further study 1

Alternative Options for Specific Scenarios

• For intra-abdominal infections due to VRE: Tigecycline 100 mg IV loading dose followed by 50 mg IV q12h 1
• For uncomplicated urinary tract infections due to VRE:
  • Fosfomycin 3 g PO single dose 1
  • Nitrofurantoin 100 mg PO every 6 hours 1
  • High-dose ampicillin (18-30 g IV daily in divided doses) or amoxicillin 500 mg PO/IV every 8 hours 1

Monitoring and Potential Adverse Effects

• Linezolid: Monitor for thrombocytopenia, especially with treatment courses >14 days, as well as gastrointestinal effects (nausea, vomiting, diarrhea), headache, and taste alteration 5, 6
• Daptomycin: Monitor creatine phosphokinase (CPK) weekly to detect potential myopathy 7
• For both agents, regular monitoring of complete blood counts is recommended 5, 6

Common Pitfalls to Avoid

• Underdosing daptomycin (doses <8 mg/kg) may lead to treatment failure and higher mortality 3, 7
• Failing to differentiate between colonization and true infection before initiating treatment 1
• Not removing central venous catheters or other potential sources of persistent infection 1
• Using tigecycline for VRE bacteremia (not recommended due to large volume of distribution and low serum levels) 1
• Neglecting to implement appropriate infection control measures to prevent VRE transmission 1